Process for preparing 5-aroyl 1,2-dihydro-3-H pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein

Abstract

5-Substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids of the formula <IMAGE> (I) wherein: X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of <IMAGE> in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo, the R substitution being at the 3, 4 or 5 position of the ring; R1 is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo, the R1 substitution being at any available position in the ring; R2 is hydrogen or lower alkyl; are prepared by beta -decarboxylation of the corresponding dialkyl-1,1-dicarboxylates. Certain substituted pyrroles are useful as intermediates for preparing the compounds of formula I.

What is claimed is: 
     
       1. A process for preparing a compound of the formula ##STR14## wherein: 
     
     
       X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of ##STR15## in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo;   R 1  is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo,   R 2  is hydrogen or lower alkyl; which comprises decarboxylating a compound represented by the formula ##STR16## wherein X and Ar are as defined previously, and R 3  is hydrogen or lower alkyl.   
     
     
       2. The process of claim 1 wherein said decarboxylation comprises treating the compound of formula II with acid. 
     
     
       3. The process of claim 2 wherein the acid is a strong mineral acid. 
     
     
       4. The process of claim 1 wherein said decarboxylation comprises treating the compound of formula II with base, and subsequently treating the resultant intermediate with acid. 
     
     
       5. The process of claim 4 wherein the base is a strong mineral base, and the acid is a strong mineral acid. 
     
     
       6. The process of claim 1 wherein the compound represented by formula II is prepared by cyclizing a compound of the formula ##STR17## wherein Ar and X are as previously defined and R 3  is lower alkyl. 
     
     
       7. The process of claim 6 wherein said cyclization is effected by treating the compound of formula H with an alkali metal hydride in an aprotic solvent. 
     
     
       8. The process of claim 6 wherein the compound of Formula H is prepared by oxidizing a compound of the formula ##STR18## wherein Ar, X and R 3  are as defined in claim 6. 
     
     
       9. The process of claim 8 wherein the oxidizing agent is m-chloroperbenzoic acid. 
     
     
       10. The process of claim 8 wherein the compound of Formula F is prepared by treating a compound of the formula ##STR19## with a lower alkyl alcohol in the presence of acid. 
     
     
       11. The process of claim 10 wherein the compound of Formula D is prepared by treating of a compound of the formula ##STR20## with an alkali metal hydride in an aprotic organic solvent, followed by treatment with spiro[2,5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione. 
     
     
       12. The process of claim 11 wherein the compound of Formula C is prepared by reacting a compound of the formula ##STR21## wherein X is as previously defined, with a compound of the formula ##STR22## and R 4  is lower alkyl in the presence of a halogenating agent. 
     
     
       13. The process of claim 12 wherein the compound of formula B is prepared by reacting a compound of the formula ##STR23## with N-halosuccinimide and dimethylsulfide. 
     
     
       14. The process of claim 13 wherein X is hydrogen or methyl, and Ar is thien-2-yl, furan-2-yl, pyrrol-2-yl or optionally substituted phenyl. 
     
     
       15. The process of claim 13 wherein the compound of Formula I is 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid. 
     
     
       16. The process of claim 6 wherein the compound of Formula H is prepared by treating a compound of the formula ##STR24## with a lower alkyl alcohol in the presence of acid. 
     
     
       17. The process of claim 16 wherein the compound of Formula G is prepared by oxidizing a compound of the formula ##STR25## 
     
     
       18. The process of claim 17 wherein the oxidizing agent is m-chloroperbenzoic acid. 
     
     
       19. The process of claim 17 wherein the compound of Formula D is prepared by treating a compound of the formula ##STR26## with an alkali metal hydride in an aprotic organic solvent, followed by treatment with spiro[2,5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione. 
     
     
       20. The process of claim 19 wherein the compound of Formula C is prepared by reacting a compound of the formula ##STR27## with a compound of the formula ##STR28## and R 4  is lower alkyl in the presence of a halogenating agent. 
     
     
       21. The process of claim 20 wherein the compound of formula B is prepared by reacting a compound of the formula ##STR29## with N-halosuccinimide and dimethylsulfide. 
     
     
       22. The process of claim 21 wherein X is hydrogen or methyl, and Ar is thien-2-yl, furan-2-yl, pyrrol-2-yl or optionally substituted phenyl. 
     
     
       23. The process of claim 21 wherein the compound of Formula I is 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid. 
     
     
       24. The process of claim 16, wherein the compound of Formula G is prepared by treating a compound of the formula ##STR30## with an alkali metal hydride in an aprotic organic solvent, followed by treatment with spiro[2,5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione. 
     
     
       25. The process of claim 24, wherein the compound of Formula E is prepared by oxidizing a compound of the formula ##STR31## 
     
     
       26. The process of claim 25 wherein the oxidizing agent is m-chloroperbenzoic. 
     
     
       27. The process of claim 25 wherein the compound of formula C is prepared by reacting a compound of the formula ##STR32## wherein X is as previously defined, with a compound of the formula ##STR33## and R 4  is lower alkyl in the presence of a halogenating agent. 
     
     
       28. The process of claim 27 wherein the compound of formula B is prepared by reacting a compound of the formula ##STR34## with N-halosuccinimide and dimethylsulfide. 
     
     
       29. The process of claim 28 wherein X is hydrogen or methyl, and Ar is thien-2-yl, furan-2-yl, pyrrol-2-yl or optionally substituted phenyl. 
     
     
       30. The process of claim 28 wherein the compound of Formula I is 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid. 
     
     
       31. The process of claim 1 wherein X is hydrogen or methyl, and Ar is thien-2-yl, furan-2-yl, pyrrol-2-yl or optionally substituted phenyl. 
     
     
       32. The process of claim 1 wherein the compound of Formula I is 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid. 
     
     
       33. A process for preparing a compound of the formula ##STR35## wherein: X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of ##STR36## in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo;   R 1  is hydrogen, lower alkyl, lower alkoxyl, carboxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo;   R 2  is hydrogen or lower alkyl; which comprises   (a) treating a compound of the formula ##STR37##  wherein X is as previously defined, with N-halosuccinimide and dimethylsulfide, followed by   (b) treating the resulting intermediate with a compound of the formula ##STR38##  wherein Ar is as previously defined and R 4  is lower alkyl in the presence of a halogenating agent, followed by   (c) treating the resulting intermediate with an alkali metal hydride in an aprotic organic solvent, followed by treatment with spiro[2,5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione followed by   (d) treating the resulting intermediate with an oxidizing agent, followed by   (e) treating the resulting intermediate with a lower alkyl alcohol in the presence of acid   (f) treating the resulting intermediate with an alkali metal hydride in an aprotic solvent, followed by   (g) treating the resulting intermediate with a base followed by   (h) treating the resulting intermediate with acid.   
     
     
       34. A process for preparing a compound of the formula ##STR39## wherein: X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of ##STR40## in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo;   R 1  is hydrogen, lower alkyl, lower alkoxyl, carboxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo;   R 2  is hydrogen or lower alkyl; which comprises   (a) treating a compound of the formula ##STR41##  wherein X is as previously defined, with N-halosuccinimide and dimethylsulfide, followed by   (b) treating the resulting intermediate with a compound of the formula ##STR42##  wherein Ar is as previously defined and R 4  is lower alkyl in the presence of a halogenating agent, followed by   (c) treating the resulting intermediate with an alkali metal hydride in an aprotic organic solvent, followed by treatment with spiro[2,5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione followed by   (d) treating the resulting intermediate with a lower alkyl alcohol in the presence of acid followed by   (e) treating the resulting intermediate with an oxidizing agent followed by   (f) treating the resulting intermediate with an alkali metal hydride in an aprotic solvent, followed by   (g) treating the resulting intermediate with a base followed by   (h) treating the resulting intermediate with acid.   
     
     
       35. A process for preparing a compound of the formula ##STR43## wherein: X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of ##STR44##  in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo;   R 1  is hydrogen, lower alkyl, lower alkoxyl, carboxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo;   R 2  is hydrogen or lower alkyl; which comprises   (a) treating a compound of the formula ##STR45##  wherein X is as previously defined, with N-halosuccinimide and dimethylsulfide, followed by   (b) treating the resulting intermediate with a compound of the formula ##STR46##  wherein Ar is as previously defined and R 4  is lower alkyl in the presence of a halogenating agent, followed by   (c) treating the resulting intermediate with an oxidizing agent, followed by (d) treating the resulting intermediate with an alkali metal hydride in an aprotic organic solvent, followed by treatment with spiro[2,5]-5,7-dioxa-6,6-dimethyloctane-4,8-dione followed by   (e) treating the resulting intermediate with an oxidizing agent, followed by   (f) treating the resulting intermediate with a lower alkyl alcohol in the presence of acid   (g) treating the resulting intermediate with an alkali metal hydride in an aprotic solvent, followed by   (h) treating the resulting intermediate with a base followed by   (i) treating the resulting intermediate with acid.